ENDOTOXIN TOLERANCE IN RATS: EXPRESSION OF TNF-α, IL-6, IL-10, VCAM-1 AND HSP70 IN LUNG AND LIVER DURING ENDOTOXIN SHOCK

Flohé, Sascha; Fernández, Emilio Domínguez; Ackermann, Markus; Hirsch, Thomas; Börgermann, Jochen; Schade, F. Ulrich

doi:10.1006/cyto.1998.0490

Cited by 74 publications

(39 citation statements)

References 51 publications

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“…Previously it has been described that IL-10 expression is increased after LPS exposure (de Waal Malefyt et al 1991;Flohe et al 1999;van der Poll et al 1994). This increased IL-10 production is endotoxin-dose dependent (de Waal Malefyt et al 1991) and is induced by pro-inflammatory cytokines including IL-1, IL-6 and TNF-α (van der Poll et al 1994;Wanidworanun and Strober 1993).…”

Section: Chapter 4 Discussionmentioning

confidence: 99%

“…No data regarding IL-10 expression in ET in equine cells exist. tolerance (Flohe et al 1999). Antibodies against IL-10 and TGF-β interfered with the development of an in vitro tolerance in human monocytes (Randow et al 1995) but did not prevent the suppression of IL-12 expression.…”

Section: Il-10mentioning

confidence: 97%

“…IL-10 downregulates the production of pro-inflammatory cytokines, mainly TNF-α, and reduces LPS toxicity and mortality in ET in mice and humans (de Waal Malefyt et al 1991;Flohe et al 1999;Howard et al 1993;. IL-10 mediates protection in the earliest phase of the LPS response but ET does not appear to be IL-10 dependent.…”

Section: Il-10mentioning

confidence: 99%

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Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

Frellstedt

McKenzie

Barrett

et al. 2012

Veterinary Immunology and Immunopathology

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Endotoxemia is responsible for severe illness in horses. Individuals can become unresponsive to the endotoxin molecule after an initial exposure; this phenomenon has been called developing a state of 'endotoxin tolerance' (ET). ET has been induced in horses in vivo; however, cytokine expression associated with ET has not been investigated. The purpose of this study was to develop and validate a method for inducing ET in equine peripheral blood mononuclear cells (PBMCs) in vitro, and to describe the cytokine profile which is associated with the ET.Blood was collected from 6 healthy horses and PBMCs were isolated. ET was induced by culturing cells with three concentrations of endotoxin given to induce ET, and evaluated after a second dose of endotoxin given to challenge the cells. The relative mRNA expression of IL-10 and IL-12 was measured by use of quantitative PCR.ET was induced in all cells (n=6) exposed to the 2-step endotoxin challenge. In PBMCs treated with 1.0 ng/ml of endotoxin followed by challenge with 10 ng/ml of endotoxin, the relative mRNA expression of IL-10 in tolerized cells was not different from positive control cells. In contrast, the relative mRNA expression of IL-12 in tolerized cells was decreased by 15-fold after the second endotoxin challenge compared with positive control cells.This experiment demonstrated a reliable method for the ex vivo induction of ET in equine PBMCs. A marked suppression of IL-12 production is associated with ET. The production of IL-10 was not altered in ET in our model.

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Section: Chapter 4 Discussionmentioning

confidence: 99%

Section: Il-10mentioning

confidence: 97%

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Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

Frellstedt

McKenzie

Barrett

et al. 2012

Veterinary Immunology and Immunopathology

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“…Perhaps the best inducer of experimental endotoxin tolerance is endotoxin itself. Pretreatment of cells or animals with a sublethal dose of LPS will result in a long-lasting refractory period during which the innate immune cells responds weakly to a second dose of LPS [37][38][39]. As many of our patients have no known LPS exposure associated with the development of immunoparalysis, it seems unlikely that this accounts for most episodes of innate immune dysfunction in the ICU.…”

Section: Mechanisms Of Immunoparalysismentioning

confidence: 99%

Immunoparalysis and Adverse Outcomes from Critical Illness

Frazier

Hall

2008

Pediatric Clinics of North America

131

108

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“…This pathologic response is mediated by cytokines such as IL-1b, IL-6 and TNF-a, which are produced under stimulation with LPS (27). The early phase of endotoxin tolerance has been found to be associated with a reduced inflammatory mediator response to endotoxin (28). The LPS-induced TNF-a and IL-1b release is decreased in endotoxin-tolerant animals (29).…”

Section: Discussionmentioning

confidence: 99%

Nucling, a novel protein associated with NF-κB, regulates endotoxin-induced apoptosis in vivo

Kim

Sakai²,

Dang³

et al. 2012

The Journal of Biochemistry

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Nucling is a proapoptotic protein that regulates the apoptosome and nuclear factor-kappa B (NF-iB) signalling pathways. Strong stimuli, such as Gramnegative bacterial lipopolysaccharide (LPS), induce the simultaneous secretion of cytokines following the activation of NF-iB. Proinflammatory cytokines can induce liver damage through several mechanisms such as increases in oxidative stress and apoptotic reactions leading to tissue necrosis. Herein, we show that Nucling-knockout (KO) mice are resistant to LPS that consistently caused mortality in wild-type (WT) counterparts. Although serum levels of cytokines such as tumour necrosis factor (TNF)-a, interleukin (IL)-1b and IL-6 did not differ significantly between WT and Nucling-KO mice after the LPS challenge, hepatocytes of Nucling-KO mice were refractory to LPS-or TNF-a-induced cell death. These results were consistent with the decreased expression of proapoptotic proteins including apoptosis-inducing factor and cleaved form of poly (ADP-ribose) polymerase and terminal deoxynucleotidyl transferase dUTP nick end-labelling positive cells in the liver of Nucling-KO mice after the administration of a lethal dose of LPS. Moreover, the upregulation of NF-iB-regulated anti-apoptotic molecules including cellular inhibitor of apoptosis (cIAP) 1 and cIAP2 was observed in the liver of Nucling-KO mice after LPS treatment. These findings indicate that the Nucling deficiency leads to resistance to apoptosis in liver. We propose that Nucling is important for the induction of apoptosis in cells damaged by cytotoxic stressors through the NF-iB signalling pathway.

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ENDOTOXIN TOLERANCE IN RATS: EXPRESSION OF TNF-α, IL-6, IL-10, VCAM-1 AND HSP70 IN LUNG AND LIVER DURING ENDOTOXIN SHOCK

Cited by 74 publications

References 51 publications

Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

Induction and characterization of endotoxin tolerance in equine peripheral blood mononuclear cells in vitro

Immunoparalysis and Adverse Outcomes from Critical Illness

Nucling, a novel protein associated with NF-κB, regulates endotoxin-induced apoptosis in vivo

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